Molecular recognition at surfaces derivatized with self-assembled monolayers

Abstract

An article suitable for use as a biosensor includes a molecule of a formula X-R-Ch adhered to a surface of the article as part of a self-assembled monolayer. X is a functionality that adheres to the surface, R is a spacer moiety, and Ch is a chelating agent. A metal ion can be coordinated by the chelating agent, and a polyamino acid-tagged biological binding partner of a target biological molecule coordinated to the metal ion. A method of the invention involves bringing the article into contact with a medium containing or suspected of containing the target biological molecule and allowing the biological molecule to biologically bind to the binding partner. The article is useful particularly as a surface plasmon resonance chip.

What is claimed is:  
     
       1. A method for making a mixed monolayer comprising self-assembled monolayer forming species, said method comprising: 
       a) providing a surface;  
       b) adding a first species having a formula X—R—NA, wherein X represents a functional group that adheres to a said surface, R represents a spacer moiety that promotes formation of a self-assembled monolayer of a plurality of said species, and NA represents a nucleic acid strand; and,  
       c) adding a second species that will form a mixed self-assembled monolayer with said first species.  
     
     
       2. A method according to  claim 1  wherein said first self-assembled monolayer forming species and said second self-assembled monolayer forming species are added together. 
     
     
       3. A method according to  claim 1  wherein said first self-assembled monolayer forming species and said second self-assembled monolayer forming species are added separately. 
     
     
       4. A method according to  claim 1  wherein said second self-assembled monolayer forming species has the formula X—R. 
     
     
       5. A method according to  claim 4  wherein said second species has the formula X—R—O(—CH 2 —CH 2 —O) n —H, where n is from 1 to 10. 
     
     
       6. A method according to  claim 1  wherein X is a sulfur containing functional group. 
     
     
       7. A method according to  claim 1  wherein R is a hydrocarbon chain optionally interrupted by at least one hetero group. 
     
     
       8. A method according to  claim 4  or  7  wherein R has the formula —(CH 2 ) n —, wherein n is from about 8 to about 24. 
     
     
       9. A method according to  claim 1  wherein said surface comprises gold. 
     
     
       10. A method according to  claim 4  wherein said second species has a formula X—R—NSBi, wherein NSBi is a non-specific inhibitor. 
     
     
       11. A method according to  claim 1  wherein said first species has a formula X—R—NA—NAB, wherein NAB represents a biological binding partner of NA. 
     
     
       12. A method according to  claim 11  wherein said NAB is a nucleic acid strand that is a binding partner of NA. 
     
     
       13. A method according to  claim 1  or  11  wherein said NA comprises a single stranded nucleic acid strand. 
     
     
       14. A method according to  claim 11  wherein said NAB comprises a single stranded nucleic acid strand.